1. Field of the Invention
The present invention relates to a new visualizing and anesthetic composition, and the process for the preparation thereof, which composition possesses useful visualizing and anesthetic activities, and, more particularly, this composition is useful for topical application to a region of mammalian skin to supply visualization to a lesion therein and to anesthetize the region for a subsequent destructive therapy.
History of the Prior Art
Certain viruses and bacteria are known to cause lesions on mammalian skin. Lesions caused by, and associated with, the human papillomavirus (HPV) are commonly known as genital warts, venereal warts or condyloma acuminata. HPV is transmitted sexually. Areas commonly affected include the cervix, vagina and external genitalia of both the female and male. Diseased tissues also develop secondary to the HPV infection. The incidence of HPV infections has increased markedly. Untreated, HPV infection can cause severe complications.
Most of the histopathologic features of HPV-related lesions correspond to the cytopathic effects of HPV on squamous epithelium in different stages of differentiation. Other features include degenerative nuclear alterations (wrinkling, pyknosis, and binucleation) of granular cells and production of excess keratin (hyperkeratosis), particularly in cutaneous warts. These genital warts or lesions are generally treated by destructive therapy, such as cryotherapy or laser vaporization in an office setting.
The prefix "cryo" denotes very low temperature. Extremely low temperature can destroy abnormal tissue. For example, cooling tissue to a temperature of -80.degree. C. will cause the treated tissue to shed off and slough away over time, producing a watery discharge.
In most cases, not only the visible lesions, but also the "invisible" lesions caused by HPV must be treated. The "invisible" lesions normally reside in normal appearing tissue adjacent to the visible lesions. Also, these "invisible" lesions are often flat, not elevated above the surface of the skin. These "invisible" lesions must first be visualized before they can be treated by any destructive therapy.
HPV infection affects the orientation of keratin filaments within the superficial layers of infected squamous epithelium. Application of dilute acetic acid (about 3-5%) to such areas causes the areas to turn white--the so-called acetowhite epithelium. In fact, benign HPV-related infections, the various grades of dysplasia, and carcinomas in situ all manifest acetowhite epithelium, particularly as seen under colposcopic visualization. It has been postulated that acetowhitening of high-grade lesions probably occurs because the osmotic dehydration accentuates the high content of optically dense chromatin in cervical intraepitheline neoplasia. On the other hand, acetowhitening of minor lesions is probably attributable to some transient reaction between acetic acid and abnormal envelope proteins in HPV-infected keratinocytes. Other grades of lesion could reflect a combination of both events. M. Coppleson, "Colposcopic Features of HPV in the Female Genital Tract" in Obstetrics and Gynecology Clinics of North America, R. Reid, Ed., Vol. 14/2, June 1987, page 476, R. Reid and P. Scalzi, Am. J. Obstet. Gynecol., Vol. 153, pages 611-618 (1985).
In addition to visualizing the lesion for therapy, some topical or local anesthetics must also be used for the comfort of the patient being treated. The use of these anesthetics is particularly desirable when treating sites which are located on the extremely sensitive external genitalia of either males or females.
Local anesthetic composition is well known in the art. U.S. Pat. No. 2,004,891 to Goldberg teaches anesthetic solution containing procaine acetate and epinephrin. U.S. Pat. No. 3,038,835 to Endres et al. discloses derivatives of 2,6-xylidine as surface anesthetic. Likewise, RESOLVE.RTM. is a commercially available product that produces surface anesthesia when applied topically to inflamed or abraded skin or to mucous membrane, such as cold sores. Each gram of RESOLVE.RTM. contains 10 mg of dyclonine hydrochloride (4'butoxy-3-piperidinopropiophenone hydrochloride).
Traditionally, the visualizing agent and the local anesthetic agent are applied separately to the regions to be subjected to destructive therapy. Commonly, the regions are "washed" with an aqueous solution of acetic acid to visualize the lesion. Then a topical anesthetic gel/ointment is applied to the same regions to prepare the regions for therapy. Occasionally, a solution of local anesthetic is injected into the regions before the therapy. The separate application of these agents, however, causes undesirable problems and complications. If the aqueous acetic acid is applied first to visualize the lesion and then followed by the application of topical anesthetic agent to induce local anesthesia, the visualizing effect of the acetic acid is hampered by the subsequent application of the anesthetic agent. Consequently, the visualization of lesions previously detected is lost. In fact, even in the absence of any other agent, the visualizing effect of the aqueous acetic acid is short-lived. If more acetic acid is reapplied to the region, the effective concentration of the topical anesthetic is reduced, lessening its anesthetic effect and causing the patient to suffer unnecessary pain.
An alternate way to apply the two agents separately is to first apply the topical anesthetic agent to the suspected region to induce topical anesthesia followed by the application of the aqueous acetic acid to visualize the lesion. However, this is also not an ideal way. Introducing aqueous acetic acid to some topical anesthetic agent usually creates a messy mix on the skin, reducing the effectiveness of the acetic acid and further obscuring the treatment site.
The effect of the traditional way of applying the visualizing agent and the local anesthetic agent separately is loss of visualization of lesions, dilution of the anesthetic effect, and obscuring the surgical field. The net result is less effective treatment of the patient accompanied by suffering greater pain than necessary.
The present invention overcomes the prior art problems as discussed above.